Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: toward combination chemotherapy of malaria through a single chemical entity.
J Med Chem
; 53(22): 8202-6, 2010 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-20979352
ABSTRACT
We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action iron(II) decomposition releases the carbonyl protease inhibitor and potentially cytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peróxidos
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Cisteína Endopeptidases
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Pró-Fármacos
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Inibidores de Cisteína Proteinase
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Chalconas
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Antimaláricos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article